After a steady decline for the last 50 years, the prevalence of cigarette smoking in the U.S. has reached a plateau of approximately 23%. Currently available treatments are not efficacious for all tobacco users. Thus, new pharmacologic agents need to be investigated to achieve the Healthy People 2010 goal of less than a 12% adult tobacco use prevalence. Bupropion, an FDA approved tobacco dependence treatment medication acts by central nervous system (CNS) dopamine and norepinephrine reuptake inhibition and through a direct inhibition of the nicotinic acetylcholine receptor. Methylphenidate, a CNS stimulant, blocks the reuptake of dopamine, serotonin and nor-epinephrine, and has a similar neurobiologic effect as nicotine. In a pilot study, methylphenidate was reported to improve symptoms of nicotine withdrawal. Thus, methylphenidate is likely to be efficacious for treating tobacco dependence rates in smokers who are attempting to stop smoking. Methylphenidate is generally well tolerated and has a low potential for abuse when used for the short term. We propose to evaluate the efficacy of an 8-week course of long acting methylphenidate (ConcertaTM) at a dose of 54-mg per day, for producing better biochemically-confirmed 7-day point prevalence tobacco abstinence rates at end of treatment compared to placebo. The study is designed as a randomized, doubleblind placebo-controlled phase II pilot study and we propose to enroll 80 smokers. If the results from this preliminary study support the performance of a larger clinical trial, then a future grant application will be submitted through the R01 research project grant mechanism. [unreadable] [unreadable] [unreadable]